Dimethylformamide → HCID 67055303, compound

HRID 602982Notes

Reaction equation

HRID 602982 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([C@@H:18]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)[C:19]3[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=3)[C:22]#[N:23])[CH2:15]2)[C:10]([F:13])([CH3:12])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:34][N:35](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:33][C:30]1[CH:29]=[CH:28][C:27]([C@@H:18]([C:19]2[CH:26]=[CH:25][CH:24]=[C:21]([C:22]#[N:23])[CH:20]=2)[N:16]2[CH2:17][CH:14]([C@@H:9]([C:4]3[CH:3]=[C:2]([CH:7]=[C:6]([F:8])[CH:5]=3)[C:34]#[N:35])[C:10]([F:13])([CH3:11])[CH3:12])[CH2:15]2)=[CH:32][CH:31]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 67055313HCID 67055313, compound

Product 1

HCID 67055303HCID 67055303, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
140 °C

Procedure

A suspension of 143 mg (0.27 mmole) of 3-[(S)-{3-[(1S)-1-(3-bromo-5-fluorophenyl)-2-fluoro-2-methylpropyl]azetidin-1-yl}(4-chlorophenyl)methyl]benzonitrile, 0.026 mg (0.216 mmole) of Zn(CN)2, 5 mg (0.005 mmole) of tris(dibenzylideneacetone)dipalladium(0) and 8 mg (0.014 mmole) of 1,1′-Bis(diphenylphosphino)ferrocene in 2.5 mL of dry DMF was degassed for 1 hat rt. Then the solution was heated at 140° C. for 17 h. The solution was concentrated under high vacuum and then was partitioned between 20 mL ether, 20 mL ethyl acetate and 10 mL water. The layers were separated and the aqueous layer was washed with two 20 mL portions of 1:1 ether-ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by preparatory TLC using 20% ethyl acetate-hexane to afford the title compound; Mass Spectrum: m/e=476 (M+1, 35Cl), 478 (M+1, 37Cl).

Workup

  1. customwas degassed for 1 hat rt
  2. concentrationThe solution was concentrated under high vacuum
  3. customwas partitioned between 20 mL ether, 20 mL ethyl acetate and 10 mL water
  4. customThe layers were separated
  5. washthe aqueous layer was washed with two 20 mL portions of 1:1 ether-ethyl acetate
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by preparatory TLC

Sources & evidence

ORD record
ord-c710b1e87e6542e5a788737e2abf3a4b
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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